Modulatory Effect Of CCK-8S On GABA-induced Depolarization From Rat Dorsal Root Ganglion

CCK is a brain-gut peptide that is abundantly distributed in both gastrointestinal tract and mammalian brain. The sulphated octapeptide fragment of cholecystokinin (CCK-8S) has been shown to be involved in numerous physiological functions such as behaviour, anxiety, learning/memory processes and neuropathic pain. CCK-8S is one of the strongest endogenous anti-opioid substances and suppresses opioid peptides-mediated'pre-synaptic inhibition'ofγ-aminobutyric acid (GABA) release. Here we provide evidence that CCK-8S modulates GABA-evoked membrane depolarization in rat dorsal root ganglion (DRG) neurons using intracellular recording technique. Results as follow:1. CCK-8S evoked membrane depolarization in rat DRG neuronsAbout 45.6%(26/57)CCK-8S (10-8 ~10-6 mol/L) evoked a depolarizing response. The membrane depolarization induced by CCK-8S was concentration dependent and abolished by prolumide (10-4 mol/L), a selective antagonist of CCK-AR (n=8). LY225910 (10-4 mol/L), a selective antagonist of CCK-BR (n=9) had no effect on CCK-8S-evoked membrane depolarisation.2. GABA-induced depolarizationThe majority of cells (90.2%,167/185) examined in the present experiment were sensitive to bath application of GABA (10-6~10-3 mol/L) with a depolarizing response. The GABA (10-6 ~10-3 mol/L)-evoked response was in a concentration-dependent manner. The threshold was about 10-6 mol/L and the maximal response was achieved by 3×10-4 mol/L GABA. The Kd value was about 3×10-5 mol/L deduced from the...